A concise update of what’s going on and what it would take to convince everyone.
Everyone wants an answer to the origin of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the culprit behind the coronavirus disease 2019 (Covid-19) pandemic. It’s not just a want but a need as well. We need to know; otherwise, we may be repeating the same mistakes and playing dice roll.
Without knowing how a pathogen of pandemic potential came to be, we won’t know how to stop the next one. Sure, we can take more stringent precautions, but we won’t know if they are the correct ones to take. So this begs the question: Is the origin of SARS-CoV-2 or Covid-19 (refers to as ‘origin’ only hereafter) solvable?
Last year's prevailing origin hypothesis was a zoonotic source, namely a jump or spillover from bats (a natural source of coronaviruses) to humans, with or without an intermediate host. But because bat-human direct contact is rare, an intermediate animal host might have mediated the spillover.
This year, however, the landscape has shifted.
In a briefing on 30th March 2021, Dr. Tedros Adhanom Ghebreyesus, the World Health Organization (WHO) Director-General, stated that all origin hypotheses remain open after reviewing the 120-page investigation report. This is indeed very courageous and honest of him. “Tedros risked his entire career to defend the integrity of the WHO,” said Jamie Metzl, Ph.D., J.D., a renowned geopolitical expert and science author.
Before going further, the lab origin hypothesis could mean two things, of which the first one is more plausible and acceptable:
- Coronaviruses sampled from nature and researched, which may or may not involve gain-of-function (GOF) experiments, might have accidentally leaked from the lab. GOF is the artificial enhancement of microbes, such as making them more infectious or deadly, to learn how dangerous they can be when they evolve in nature. But it’s debatable if GOF research refers to microbes that affect humans only or all species, which is why the U.S. has denied that they funded GOF research in the Wuhan Insitute of Virology (WIV) that studies animal coronaviruses.
- Bioengineering from scratch to create a bioweapon that might have leaked accidentally or deliberately. Bioengineering creates or designs while gain-of-function modifies or improves existing microbes.
The briefing marks the first transition into a more open discussion of the lab origin hypothesis, which was considered taboo and a conspiracy that fueled anti-Asian racism last year. Such discussion has, indeed, gained remarkable traction and, surprisingly, even acceptance by many.
For instance, I wrote an article in April 2021 that summarizes the 120-page WHO-China joint investigation report, alongside its flaws and criticisms, and details the arguments for and against the lab origin hypothesis, as well as what’s the step forward in explaining the origin mystery.
But it wasn't until next month that two events triggered the widespread recognition of the lab origin hypothesis. One is the long-form piece of Nicholas Wade, author of numerous books and a veteran science writer and editor, that describes the circumstantial evidence — from both the political and scientific sides — for the lab origin hypothesis. The second event is an open letter from 18 top scientists — e.g., Prof. Akiko Iwasaki, Prof. Ralph S. Baric, and Prof. David A. Relman — to the journal Science, which calls for further investigations into the lab origin hypothesis.
Even Anthony S. Fauci, MD, the U.S. President’s chief medical advisor and director of the National Insitute of Allergy and Infectious Disease, who previously dismissed the lab origin hypothesis, now thinks otherwise.
When asked, “Are you still confident that it [SARS-CoV-2 or Covid-19] developed naturally?” Dr. Fauci replied: “No actually, I am not convinced about that, I think we should continue to investigate what went on in China until we continue to find out to the best of our ability what happened…Certainly, the people who investigated it say it likely was the emergence from an animal reservoir that then infected individuals, but it could have been something else, and we need to find that out.”
The evidence — all circumstantial, however — for the lab origin is rather substantial and even convincing, which many writers have detailed, such as Wade, Yuri Deigin, Donald McNeil, Nicholson Baker, Matt Ridley, Jamie Metzl, Rowan Jacobson, Milton Leitenberg, Allen Rodrigo, and Katherine Eban (as well as myself). After going through them, here are the key points:
- The WHO-China investigation failed to find any evidence of SARS-CoV-2 in nature. China tested over 80,000 animal samples that might harbor traces of SARS-CoV-2, and all came back negative. Only a few non-animal samples (e.g., door handles and object surfaces) from the market were tested positive by PCR; this suggests that infections took place, but not from the animals. By contrast, no samples from labs in Wuhan, where the first Covid-19 outbreak began, have been formally investigated.
- Accidental lab leaks of dangerous microbes have happened many times before, even in top laboratories like the U.S. Centers for Disease Control and Prevention (CDC). The prior SARS-1, for example, has leaked for at least six separate occasions after its outbreak ended in 2003.
- The present gain-of-function research has advanced to the point where it’s indistinguishable from natural evolution. So, we can’t tell if a microbe like SARS-CoV-2 (or its ancestor) has been enhanced in the lab or not. The WIV has published gain-of-function coronavirus research performed in biosafety level 2 and 3 (BSL2 and BSL3) labs. And BSL2 is not stringent. Research on SARS and MERS coronaviruses, for example, must be performed at BSL3; Ebola and Marburg viruses at BSL4 (the highest level), yet lab accidents occurred at BSL3 and BSL4 before.
- The U.S. Intelligence Community claims that three workers in the WIV got sick with something that resembles Covid-19 in November 2019, right before the outbreak. This contradicted the initial claims of Dr. Shi Zhengli, head of the WIV, that they were zero infections among their staff and students before January 2021.
- The WIV’s database that stores a huge collection of coronavirus genomes was locked in September 2019 and taken down during the spring of 2020 to allegedly protect against hackers during the pandemic. But the outbreak started in December 2019 and declared a pandemic in March 2020. This database was not examined during the WHO-China joint investigation.
- If the origin SARS-CoV-2 lies in nature, notably bats, Yunnan should have been ground zero. The bat caves are in Yunnan, and the bats don’t travel to Wuhan, where the Covid-19 outbreak started. In Wuhan, there are labs and wet markets that sell wildlife products. (Bats were not sold in the market when the outbreak started.) As stated in #1, no traces of SARS-CoV-2 were detected among the tens of thousands of animal samples tested, which included those in the market.
- Although debatable, political aspects might also be regarded as circumstantial evidence. China is secretive by default, known for suppressing journalists and scientists from probing and reporting sensitive issues. For instance, China downplayed case counts and forbade WHO researchers from visiting the site of the SARS outbreak in 2002. And China did the same thing again in 2020 for SARS-CoV-2. So, cover-ups of accidental lab leak of microbes, which doesn't have to be SARS-CoV-2, are imaginable. Besides, a few researchers who were quick to dismiss the lab origin hypothesis as absurd built their lucrative careers around coronavirus research, a clear conflict of interest.
All that said, the lab origin hypothesis is not without flaws. Donal G. McNeil, a seasoned science and health reporter, Nature (a leading scientific journal), and a few others, including myself, have detailed them. And here are the main points:
- Although both lab and natural origin are possible, the latter is more probable. Lab leak scenario depends on a single event — a lab mistake. (This is unless it’s a deliberate release, but it’s silly to release it in Wuhan then, where the very WIV is located.) On the other hand, the spillover from nature scenario can occur whenever there’s animal-human contact — such as in any of the numerous farms and markets in China.
- Lab leak scenario depends on the event that researchers were working on live SARS-CoV-2 (or its ancestor) virions, which higher-ups must have been aware of. And Dr. Shi, the WIV’s head, has claimed that they have not worked on any viruses similar to SARS-CoV-2 before the outbreak.
- While the fact that Chinese authorities ordered labs to destroy samples that might contain SARS-CoV-2 may seem like a cover-up, it may also be a public health decision to prevent further outbreaks. Moreover, China’s uncooperativeness during the early pandemic may not have malicious intent but rather a defensive behavior against insults from the U.S. Trump administration. Not to mention that China is always secretive about sensitive topics, Covid-19 or not.
- Although certain peculiar elements in the SARS-CoV-2 genome may signify manipulation or enhancement via GOF technology, this is just one way of interpretation. Another interpretation is that because they are so peculiar, only mother nature is smart enough to design them.
- Historically, large-scale outbreaks have come from nature. For example, SARS and MERS coronaviruses jumped from bats to an intermediate host (i.e., civet for SARS and camel for MERS) and to humans. Other human viruses— Ebola, West Nile, rabies, and influenza— also have a natural origin.
- Although China failed to find any traces of SARS-CoV-2 in the tens of thousands of animal samples tested, it may be quick to rule it as evidence of absence. More sampling work — perhaps even beyond China — may still be needed. It took 14 years to get a clear picture of the origin of SARS-1, 20 years for human immunodeficiency virus (HIV), and x years for Ebola virus with unclear origin to this day.
Overall, neither the natural nor lab origin hypotheses are proven. That’s why they are only hypotheses, not theories. So, at this point, we can't afford to ask what is the true origin, but we can ask what it will take to answer that.
An independent, unbiased investigation into the labs in Wuhan would be needed to confirm or disconfirm the lab origin hypothesis. That means examining everything in suspicion — lab records and data, animal and non-animal samples, lab equipment functionality, etc. But this has not been and may never be done. After all, allowing such investigation is to leak sensitive and classified information. No country would be happy to allow that, especially when the WIV works closely with the Chinese military, according to the U.S. government. (But the WIV’s head, Dr. Shi, has denied any military involvement in WIV.)
Even if such independent investigation is somehow allowed, nearly two years have passed since the Covid-19 outbreak in Wuhan in December 2019. That’s plenty of time to get rid of evidence if there’s a need to do so. This means that not everyone will be convinced if an independent investigation in the future says that the lab origin hypothesis is false.
This is unless the Chinese authorities were unaware that SARS-CoV-2 got leaked from Wuhan labs, only to be caught by independent investigators, or that China comes clean and admits that the lab origin hypothesis is true. Such scenarios would indeed convince everyone, but we all know they are highly improbable. The pandemic has cost us far too much: the loss of millions of lives; the economic disruption that further widens the wealth disparity, and the physical (e.g., long-COVID and post-ICU syndrome) and mental (e.g., social isolation and bereavement) health burden. It may be wishful thinking that someone would step up and take responsibility for the disaster caused should the lab origin hypothesis is true.
The other scenario is that China authorities found evidence of SARS-CoV-2 or its direct ancestor in an animal reservoir in nature. But as long Wuhan labs have not been subjected to independent investigations, not all will be convinced if China is transparent and honest. Skeptics will suspect if China is planting misleading evidence to shift attention away from the labs. (The pangolin, for example, was nearly accepted as the intermediate host of SARS-CoV-2 but turned out to be untrue due to flawed analyses.) Skeptics would also question if labs have sampled such an animal reservoir that carries SARS-CoV-2 (or its ancestor) and leaked it out by accident.
Therefore, the lab origin hypothesis has to be disproven to restore trust in China. The circumstantial evidence for this hypothesis has become fairly substantial to ignore. But disproving this hypothesis may be impossible since the possibility that evidence might have been erased already exist. It may already be too late to send independent investigators to labs in Wuhan and expect transparent results that would convince everyone.
“I don’t know if we will ever find a smoking gun, especially if it was a lab accident. The stakes are so high now. It would be terrifying to be blamed for millions of cases of COVID-19 and possibly up to a million deaths by year end, if the pandemic continues to grow out of control,” Alina Chan, Ph.D., a molecular biologist at the Broad Institute of MIT and Harvard, said last year. And, clearly, the stakes only got so much higher this year.
“With every passing day and week, the kinds of information that might prove helpful will have a tendency to dissipate and disappear,” David A. Relman, M.D., professor of medicine and immunology & microbiology at Stanford University School of Medicine, said. “The world ages and things get moved, and biological signals degrade.”
In the end, the true origin of SARS-CoV-2 may forever remain obscure, and many will forever remain skeptical no matter how things play out. And because we don’t know how this pandemic started, we also don’t how to prevent the next one. We will have to roll the dice and brace ourselves for the unknown.
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